Substitution of abnormal stem cells with healthy cells has been accomplished clinically through hematopoietic stem cell (HSC) transplantation for more than 50 years. Umbilical cord blood (UCB) is an alternative to bone marrow or peripheral blood HSC source for patients with hematologic diseases who need allogeneic hematopoietic cell transplantation. The first UCB transplantation was performed in 1988 for a child with Fanconi anemia. The field of UCB banking and transplantation has grown exponentially ever since. However, the number of banked UCB in both public and private banks is much lower than available umbilical cords. High costs and complex procedures are two major hurdles to be overcome. Recently, we have developed an innovative microbubble-based technology for rare cell isolation in blood that can help resolve these issues. We use perfluorocarbon-filled microbubbles (MBs), which have been used as a safe ultrasound contrast agent. Therefore, this material would be suitable for isolating cells for therapeutic applications. Here we propose to develop a close system that can be intuitively operated without the need of specialized equipment. By target isolation of HSC, this technology can reduce volume of a unit of cord blood (>20 ml) to be stored in a designed container with much small volume (< 1 ml). The simplicity of the procedure and reduction of the cost may revolutionize the UCB banking industry. In Phase 1, we will develop standardized methods for efficient HSC isolation using our proposed approach. In Phase 2, we will apply this established protocol to develop commercial products for clinical and research uses.